组胺可能是一种新的外周交感神经递质
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摘要
本实验研究利用原位杂交组织化学技术和地高辛标记的寡核苷酸探针检测组氨酸脱羧酶(Histidine Decarboxylase,HDC)mRNA在豚鼠颈上神经节中的表达，利用免疫组织化学技术检测组胺在正常豚鼠和利血平化豚鼠颈上神经节中的分布，采用离体心房灌流技术和荧光分析技术检测组胺在正常豚鼠和利血平化豚鼠心脏交感神经末梢组胺释放的规律。寻找心脏组胺受体的内源性配体的来源和分布，探讨可能存在的组胺H_3受体作为自身受体对心脏交感神经释放去甲肾上腺素负反馈调控路径，以期为临床治疗心血管疾病提供理论基础和新的思路。
一 HDC mRNA在豚鼠颈上神经节中表达的研究
在基因库内挑选小鼠HDC的cDNA序列，用BLAST软件进行分析该核苷酸序列，选择保守性较好的核苷酸序列并确定可用于检测HDC mRNA的寡核苷酸探针序列。利用原位杂交组织化学技术检测HDC mRNA在豚鼠颈上神经节中的表达。结果显示：豚鼠颈上神经节中有较多的神经元呈HDC阳性，HDC mRNA阳性信号在大、小细胞的细胞浆内均有分布，在细胞核内没有检测到阳性信号。由于HDC能催化组氨酸脱羧基形成组胺，提示组胺可在颈上神经节细胞的细胞浆内合成。
束四吊医大学项士研兑生论文
一
二 组胺和酪氨酸羟化酶（Tyrosine hydrorylasc＊H）在豚鼠
颈上神经节中共存的研究
利用荧光双标免疫组织化学技术和激光共聚焦显微镜，分别观察组
肢和TH在正常豚鼠和化学法损毁后的豚鼠颈上神经节中的共存现象。结
果显示：TH阳性细胞（应用异硫氰酸二抗抗酪氨酸羟化酶，发绿色荧光）
和组胺阳性细胞（应用四乙基异硫氰酸罗达明二抗抗组胺，发红色荧光）
在正常豚鼠颈上神经节中均有大量分布，在大型和小型细胞内均发现有
双标阳性信号，其中TH阳性信号均匀分布在胞浆内，而组胺阳性信号主
要分布在近胞膜处的胞浆内。化学损毁颈上神经节的交感神经细胞后未
发现有阳性信号的细胞，提示在豚鼠颈上神经节中组胺和TH共存于交感
神经细胞内。
三 豚鼠心脏交感神经末梢释放组胺规律的实验研究
离体灌流正常豚鼠和利血平化豚鼠的右心房，不应期电场刺激诱发
心房交感神经末梢释放去甲肾上腺素等神经递质，应用荧光分光光度计
检测灌流液内组胺释放量的变化。结果为：正常组的豚鼠心房经场刺激
后检测到了组胺的释放量为 109石7土48．88 ＂g／ml，n＝8，化合物 48用0可
以使心房肥大细胞脱颗粒释放组胺为 297．50士88石8 ngiml，n－8，肥大细
胞组胺耗竭后仍检测到了不应期电场刺激诱发的组胺释放：利血平耗竭
心房交感神经系统的神经递质后与正常组相比较组胺释放量明显减少
（29刀 土ZI二9 ＂g／ml， n－8＼提示在豚鼠心房交感神经系统可能有组胺的
存在。
The histaminergic nerves exit in the hypothamus mainly and the histaminergic nervous system was found hi the brain, but there was little study on the presence of histamine in peripheral nerve system. The histidine decarboxylase is the only enzyme that catalyzes histidine into histamine, so it is regarded as the marker of the histaminergic cell. Accordingly, using in situ hybridization histochemistry technology with specific oligonucleotide probe and immunohistochemistry technology with anti-histamine antibody, the histidine decarboxylase rnRNA hybridization signal and histamine positive signal were detected in the superior cervical ganglia. The releasing of histamine was also detected in the isolated atrium of guinea pig, but it reduced greatly in the isolated atrium of resipined guinea pig. Therefore, histamine may be synthesized in the sympathetic nerve and modulates important neurotransmission such as NE in the heart, participates the normal physiology processes.
1 The expression of histidine decarboxylase (HDC) in the superior cervical ganglion of guinea pig
Using in situ hybridization histochemistry technology with specific
oligonucleotide probe, the postival signal was detected in the suprior cervical ganglion (SCO) of guinea pig. There were lots of cells containing the HDC, and the postival signal was detected in both of large and small cells. Because the HDC is the only enzyme which catalyzes histidine into histamine, it seems that the histamine can been synthesed in the SCO.
2 The coexistance of histamine and tyrosine hydroxylase(TH) in the superior cervical ganglion of guinea pig
Using immunohistochemistry technology with anti-histamine antibody and anti-TH antibody^ the fluorescent antibody: fluorescein isothiocyanate and tetramethylrhodamine isothiocyanat, both immunoreactive materials were detected in the same cells of guinea pig superior cervical ganglion. The TH immunoreactive substance distributed in cytoplasm steadly with negative nuclei, while the histamine immunoreactive substance distributed in cytoplasm nearby the plasmalemma. After chemical destroy of the guinea pig SCO's sympathetic neuron with 6-(OH)-DA, the immunoreactive materials were hardly detected, it indicated that histamine exists in the sympathetic neuron.
3 The releasing of histamine in the sympathetic nerve of guinea pig isolated atrium
It has been reported that histamine had been present in guinea pig hearts, in order to study whether histamine exists in the sympathetic nerve of guinea pig heart, we used spectrofluorometer to detect the releasing of histamine from isolated guinea pig atria stimulated by field electronic stimulator(109.67 ?8.88 ng/ml, n=8). Compound 48/80(100 ng/ml) was added 2-3 times to the isolated guinea pig atria to degrenuate histamine from mast cell(297.50?
88.68 ng/ml , n=8) totally, then histamine was still detected using spectrofluorometer, and the releasing of histamine was reduced in the respined isolated guinea pig atria(29.17?1.29 ng/ml. n=8) comparing with the normal group. So it can be concluded that histamine presents in the sympathetic nerve of guinea pig atrium.
一 HDC mRNA在豚鼠颈上神经节中表达的研究
在基因库内挑选小鼠HDC的cDNA序列，用BLAST软件进行分析该核苷酸序列，选择保守性较好的核苷酸序列并确定可用于检测HDC mRNA的寡核苷酸探针序列。利用原位杂交组织化学技术检测HDC mRNA在豚鼠颈上神经节中的表达。结果显示：豚鼠颈上神经节中有较多的神经元呈HDC阳性，HDC mRNA阳性信号在大、小细胞的细胞浆内均有分布，在细胞核内没有检测到阳性信号。由于HDC能催化组氨酸脱羧基形成组胺，提示组胺可在颈上神经节细胞的细胞浆内合成。
束四吊医大学项士研兑生论文
一
二 组胺和酪氨酸羟化酶（Tyrosine hydrorylasc＊H）在豚鼠
颈上神经节中共存的研究
利用荧光双标免疫组织化学技术和激光共聚焦显微镜，分别观察组
肢和TH在正常豚鼠和化学法损毁后的豚鼠颈上神经节中的共存现象。结
果显示：TH阳性细胞（应用异硫氰酸二抗抗酪氨酸羟化酶，发绿色荧光）
和组胺阳性细胞（应用四乙基异硫氰酸罗达明二抗抗组胺，发红色荧光）
在正常豚鼠颈上神经节中均有大量分布，在大型和小型细胞内均发现有
双标阳性信号，其中TH阳性信号均匀分布在胞浆内，而组胺阳性信号主
要分布在近胞膜处的胞浆内。化学损毁颈上神经节的交感神经细胞后未
发现有阳性信号的细胞，提示在豚鼠颈上神经节中组胺和TH共存于交感
神经细胞内。
三 豚鼠心脏交感神经末梢释放组胺规律的实验研究
离体灌流正常豚鼠和利血平化豚鼠的右心房，不应期电场刺激诱发
心房交感神经末梢释放去甲肾上腺素等神经递质，应用荧光分光光度计
检测灌流液内组胺释放量的变化。结果为：正常组的豚鼠心房经场刺激
后检测到了组胺的释放量为 109石7土48．88 ＂g／ml，n＝8，化合物 48用0可
以使心房肥大细胞脱颗粒释放组胺为 297．50士88石8 ngiml，n－8，肥大细
胞组胺耗竭后仍检测到了不应期电场刺激诱发的组胺释放：利血平耗竭
心房交感神经系统的神经递质后与正常组相比较组胺释放量明显减少
（29刀 土ZI二9 ＂g／ml， n－8＼提示在豚鼠心房交感神经系统可能有组胺的
存在。
The histaminergic nerves exit in the hypothamus mainly and the histaminergic nervous system was found hi the brain, but there was little study on the presence of histamine in peripheral nerve system. The histidine decarboxylase is the only enzyme that catalyzes histidine into histamine, so it is regarded as the marker of the histaminergic cell. Accordingly, using in situ hybridization histochemistry technology with specific oligonucleotide probe and immunohistochemistry technology with anti-histamine antibody, the histidine decarboxylase rnRNA hybridization signal and histamine positive signal were detected in the superior cervical ganglia. The releasing of histamine was also detected in the isolated atrium of guinea pig, but it reduced greatly in the isolated atrium of resipined guinea pig. Therefore, histamine may be synthesized in the sympathetic nerve and modulates important neurotransmission such as NE in the heart, participates the normal physiology processes.
1 The expression of histidine decarboxylase (HDC) in the superior cervical ganglion of guinea pig
Using in situ hybridization histochemistry technology with specific
oligonucleotide probe, the postival signal was detected in the suprior cervical ganglion (SCO) of guinea pig. There were lots of cells containing the HDC, and the postival signal was detected in both of large and small cells. Because the HDC is the only enzyme which catalyzes histidine into histamine, it seems that the histamine can been synthesed in the SCO.
2 The coexistance of histamine and tyrosine hydroxylase(TH) in the superior cervical ganglion of guinea pig
Using immunohistochemistry technology with anti-histamine antibody and anti-TH antibody^ the fluorescent antibody: fluorescein isothiocyanate and tetramethylrhodamine isothiocyanat, both immunoreactive materials were detected in the same cells of guinea pig superior cervical ganglion. The TH immunoreactive substance distributed in cytoplasm steadly with negative nuclei, while the histamine immunoreactive substance distributed in cytoplasm nearby the plasmalemma. After chemical destroy of the guinea pig SCO's sympathetic neuron with 6-(OH)-DA, the immunoreactive materials were hardly detected, it indicated that histamine exists in the sympathetic neuron.
3 The releasing of histamine in the sympathetic nerve of guinea pig isolated atrium
It has been reported that histamine had been present in guinea pig hearts, in order to study whether histamine exists in the sympathetic nerve of guinea pig heart, we used spectrofluorometer to detect the releasing of histamine from isolated guinea pig atria stimulated by field electronic stimulator(109.67 ?8.88 ng/ml, n=8). Compound 48/80(100 ng/ml) was added 2-3 times to the isolated guinea pig atria to degrenuate histamine from mast cell(297.50?
88.68 ng/ml , n=8) totally, then histamine was still detected using spectrofluorometer, and the releasing of histamine was reduced in the respined isolated guinea pig atria(29.17?1.29 ng/ml. n=8) comparing with the normal group. So it can be concluded that histamine presents in the sympathetic nerve of guinea pig atrium.
引文
1． Ash ASF and Schild HO. Receptors mediating some actions of histamine. BrJ.Pharmacol, 1966;27:427~439
2． Black JW, Shankley NP.How does gastrin act to stimulate oxyntic cell secretion? Trends Pharmacol.Sci,1987;8:486~490
3． Arrang JM, Garbarg M, Schwartz JC. Autoinhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature, 1983;302:832~837
4． Yamasaki T, Tamai I, Matsumura Y. Activation of histamine H3 receptors inhibits renal noradrenergic neurotransmission in anesthetized dogs. Am J Physiol Regul Integr Comp Physiol, 2001; 280(5) :R 1450-1456
5． Black JW, Duncan AM, Durant J et al. Definition and antagonism of histamine H2-receptors. Nature, 1972;236:385~390
6． Raible DG, Lenahan T, Fayvilevich Y et al. Pharmacologic characterization of a novel histamine receptor on human eosinophils. Am.J.Respi.Crit.Care.Med, 1994; 149(6) : 1506-1511
7． 韩济生，神经科学纲要，北京：北京医科大学、中国协和医科大学联合 出版社,1993:419-421
8． Garbarg M, Barbin G, Feger J et al. Histaminergic pathway in rat brain evidenced by lesions of the medial forebrain bundle. Science, 1974; 186:833-835
9． Schwartz JC, Pollard H, Quach TT. Histamine as a neurotransmitter in mammalian brain: neurochemical evidence. J Neurochem, 1980; 35: 26-33
10． Hough LB. Cellular location and possible functions for brain histamine: recent progrees. Prog Neurobiol, 1988; 30: 469-505
11． Schwartz JC, Arrang JM, Garbarg M et al. Histaminergic traminergic transmission in the mammalian brain. Physiol Rev, 1991; 71: 1~15
12． Wada H, Inagaki N, Yamatodani A et al. Is the histaminergic neuron system a regulatory center for whole-brain activity? TINS,1991; 14: 415-418
13． Pollard H, Schwartz JC. Histamine neuronal pathways and their functions. Trends Neurosci, 1987; 10: 86~89
14． Alexandra AR, henk T, Edwin W et al.Pharmacological characterization of the histamine H3 receptor in the rat hippocampus Brain Res, 1998; 788; 179-186
15． Nishino S, Fujiki N, Ripley B et al. Decreased brain histamine content in hypocretin/oxexin receptor 2 mutated harcoleptic dogs. Neurosci Lett, 2001;313(2) :125~128
16． .Lozeva V, valjakka A, Anttjla E et al. Brain histamine levels and neocotical slow-wave activity in rats with portancaval anastomosis. Hepatology, 1999; 299(2) : 340-346
17． Gupta MA, Guptat AK. The use of antidepressant drugs in dermatology. J Eur Acad Dermatol Venereol, 2001; 15(6) : 512-518
18． Twmisto L, Lozeva V, Valjakka A et al. Modifying effects of histamine on circadian rhythms and neuronal excitability. Behav Brain Res, 2001; 124(2) ; 129-1351
19． Passani MB, Cangioli L, Baldi E et al. Histamine H3 receptor mediated impairmen of contextual fear conditioning and in vivo inhibition of
cholinergic transmission in the rat basolateral anygdala, Eur J neurosci, 2001; 14(9) : 1522-1532
20． Bacciottini L, passani MB, Mannaioni PF et al. Interactions between histaminergic and cholinergic systems in learning and memory. Behav Brain Res,2001; 124(2) : 183-194
21． Phjlippu A, Prast H. Importance of histamine in modnlatory processes, locomotion and memory. Behav Brain Res, 2001; 124(2) : 151-159
22． Sharma HS, Cervo S, Nararro J. Role of histamine in pathophysiology of heart stress in rats. Agents Actions Suppl, 1991; 33: 97~102
23． Bealer SL. Central neuronal histamine contributes to cardiovascular regulation. News Physiol Sci, 1999; 14:100~105
24． Mobarakeh JI, Sakurada S, Katsuyama S et al. Role of histamine H1 receptor in pain perception: a study of the receptor gene knockout mice. Eur J Pharmacol, 2000; 391(1-2) : 81-89
25． Srurman G, Freeman P, Quinn L. Histamine H1 receptor antagonists potentiate seizures in the EL(epilepsy-like) mouse model of temporal lobe epilepsy. Inflamm Res, 2001; 2: 80-81
26． Vohora D, Pal SN, Pillai KK. Histamine and selective H3 receptor ligands: a possible role in the mechanism and management of epilepsy. Pharmacol Biochem Behav, 2001; 68(4) : 735-741
27． Kjaer A, Knigge V, Jorgensen H et al. Dehydration-induced vasopressin secretion in humans: involvement of the histaminergic system. Am J Physiol Endocrinol Metab,2000; 279(6) : E1305-1310
28． Lopes JA, Ramis C, Nicolau MC et al. Histamine drugs in the rat caudate nucleus: effects on learned helplessness. Pharmacol Biochem Behav,1993;
45(2) : 275-282
29． Anthonisen M, Knigge V, Kjaer A et al. Histamine and prostaglandin interaction in the central regulation of ACTH secretion. Neuroendocrinology, 1997; 66(2) : 68-74
30． Giotti A, Guidotti A, Mannaioni PF et al. The influences of andrenotropic drugs and noradrenaline on the histamine release in cardiac anaphylaxis in vitro.J Physiol, 1966; 184(4) : 924-941
31． Triggiani M, Genovese A, Vigorito C et al. Histamine and human heart Int Arch Allergy Appl Immunol, 1985; 77(1-2) : 174-176
32． Rydzynski K, Kolago B, Zaslonka J et al. Distribution of mast cells in human heart auricles and correlation with tissue histamine. Agents Actions. 1988; 23(3-4) :273~275
33． Harvey SC. Comparative regional and subcellular distributions of histamine and norepinephrine in the hearts of rats, mice, guinea pigs, rabbits and dogs. Jpn Heart J,1978; 19(1) : 125-135
34． Rioux F, Kerouac R, St-Pierre S. Characterization of the histamine releasing effect of neurotensin in the rat heart. Peptides, 1985 ; 6(1) :121-125．
35． Yamatodani A, Maeyama K, Watanabe T et al. Tissue distribution of histamine in a mutant mouse deficient in mast cells: clear evidence for the presence of non-mast-cell histamine. Biochem Pharmacol,1982; 31(3) :305~309
36． Patella V, Marino I, Lamparter B et al. Immunologic and non-immunologic release of histamine and tryptase from human heart mast cells. Inflamm Res, 1995; 44 (Suppl) 1:S22-23
37． Masini E, Giannella E, Bianchi S et al. Histamine and lactate dehydrogenase (LDH) release in ischemic myocardium of the guinea pig. Agents Actions, 1987; 20(3-4) : 281-283
38． Negulescu P.A. and Machen T. Intracellular Ca2+ regulation during secretogogue stimulation of the pariental cell. Am.J.Physiol, 1988; 254:C130~140
39． Johnson CL, Mizoguchi H. The interaction of histamine and guanylnucleotides with cardiac adenylate cyclase and its relationship to cardiac contractility. J Pharmacol Exp Ther, 1977; 200:174~186
40． Amerinin S, Franconi F, Ledda F et al. H1 and H2 receptor in the guinea pig heart: an electrophysiological study. Agents Actions ,1982; 12:10~18
41． Chand N, Eyre P. Classification and biological distribution of histamine receptor. Agents Actions, 1975; 5:277~295
42． Luo XX, Song L, Jiang YP et al. Inhibition of sympathetic neurotransmission via NEM-sensitive H1 receptors in the guinea pig vas deferens. Meth Find Exp Clin Pharmacol, 1994; 16(3) : 185~189
43． Fatma A, Ercan Z, Purker PK. A marked H1 receptor mediated vasodilator effect of histamine in the isolated perfusal heart. Eur J Pharmacol, 1984; 97: 265-271
44． Gupta MK, Gupta P, Rezai F et al. Histamine--can it cause an acute coronary event? Clin Cardiol, 2001; 24(3) :258-259
45． Kalsner S, Ricard R. Coronary arteries of cardial patients are hyperreactivity and contain stores of amines: a mechanism coronary spasm. Science, 1984; 223:1435-1436
46． 汪昌树，刘冰怀，冠心病患者血浆组胺的变化及临床意义.广东医学,
1994; 15(3) : 154-155
47． Byron JW. Mechanism of histamine H2 receptor induced cell-cycle changes in the bone marrow stem cell. Agents Actions, 1977; 7: 209~214
48徐有恒,蒋德昭,王绮如,等,组胺H1和H2受体激动剂对多能造血 干细胞(CFU-S)细胞周期状态的影响.中国科学B辑,1988; 1: 71-73
49． Schneider E, Piquet-Pellorce C, Dy M et al. New role for histamine in interleukin-3-induced proliferation of hematopoietic stem cells. J Cell Phgsiol, 1990; 193: 337-343
50． Corbel S, Schneider E, Lemoine FM et al. Murine hematopoietic progenitors are capable of both histamine synthesis and uptake. Blood, 1995; 86: 531-535
51． Masini E, Di Bello MG, Raspanti S et al. The role of histamine in platelet aggregation by physiological and immunological stimuli. Inflamm Res, 1998; 47(5) : 211-220
52． Mannaioni PF, Pistelli A, Gambassi F et al. Definition of platelet-derived histamine-releasing factor and histaminergic receptors modulating platelet aggregation. Int Arch Allergy Appl Immunol, 1991; 94(1-4) :301-302
53． Masini E, Pistelli A, Gambassi F et al. Definition of platelet-derived histamine releasing factor (PDHRF) and histaminergic receptors modulating platelet aggregation. Adv Prostaglandin Thromboxane Leukot Res, 1991;218:533-536
54． Saxena SP, McNicol A, Brandes LJ et al. A role for intracellular histamine in collagen-induced platelet aggregation. Blood, 1990 ; 75(2) :407-414．
55． Levi R, Zavecz JH. Acceleration of idioventricular rhythms by histamine in guinea pig heart: mediation by H2 receptors. Circ Res,1979;
44(6) :847~855
56． Reinhardt D. Cardiac actions of histamine. Anaesthesist, 1979;28(2) :67~ 77
57． Levi R, Chenouda AA, Trzeciakowski JP et al. Dysrhythmias caused by histamine release in guinea pig and human hearts. Klin Wochenschr, 1982 1;60(17) :965~971
58． Kashani M, Khoyi MA, Zendehrouh R et al. The effect of histamine on the plasma potassium level and electrocardiogram of dogs. J Med, 1972; 3(2) : 103-108．
59． Doenicke A, Moss J, Toledano A et al. Administration of H1 and H2 antagonists for chemoprophylaxis: a double-blind, placebo-controlled study in healthy volunteers. J Clin Pharmacol, 1997; 37(2) : 140-146．
60． Nishimoto M, Hashimoto H, Ohmura T et al. Effects of astemizole on ventricular activation delay and RT intervals in a canine myocardial infarction model. Biol Pharm Bull, 1997; 20(9) : 1020-1023
61． Vleeming W, van Rooij HH, Werner J et al. Characterization and modulation of antigen-induced effects in isolated rat heart. J Cardiovasc Pharmacol, 1991 ; 18(4) :556-565
62． Assem ES. Anaphylactic reactions affecting the human heart. Agents Actions, 1989 ;27(1-2) :142-145
63． Steinberg MI,Holland DR.Separate receptors mediating the positive intropic and chronotropic effect of histamine in guinea pig atria. Eur J.Pharmacol, 1975 ; 34:95-104
64． Lin RY, Schwartz LB, Curry A et al. Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based
study.J Allergy Clin Immunol, 2000 ; 106(1 Pt 1) :65~71
65． Skuma I, Gross SS, Levi R. Positive intropic effect of histamine on guinea pig left atrium: H1 receptor induced stimulation of phosphoinositide turnover. J Pharmacol. Exp. Ther, 1988; 247:466-472
66． Passalacqua G, Bousquet J, Bachert C et al. The clinical safety of Hi-receptor antagonists. An EAACI position paper. Allergy, 1996; 51(10) :666~675
67． Ooie T, Saikawa T, Kara M, Ono H et al. H2-blocker modulates heart rate variability. Heart Vessels, 1999;14(3) :137~142
68． Malinowska B, Godlewski G and Schlicker E. Histamine H3 receptors-general characterization and their function in the cardiovascular system.J Physiol Pharmacol, 1998 ; 49(2) :191~211．
69． Endou M, Poli E and Levi R. Histamine H3-receptor signaling in the heart: possible involvement of Gi/Go proteins and N-type Ca++ channels. J Pharmacol Exp Ther,1994 ;269(1) :221~229
70． Malinowska B, Godlewski G and Schlicker E. Histamine H3 receptors-general characterization and their function in the cardiovascular system. J Physiol Pharmacol, 1998 ;49(2) :191-211
71． Imamura M, Seyedi N, Lander HM et al. Functional identification of histamine H3-receptors in the human heart. Circ Res, 1995;77(1) :206~ 210
72． Silver RB, Poonwasi KS , Seyedi N et al. Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings. Proc Natl Acad Sci U S A, 2002;99(1) :501-506
73． Schlicker E, Kathmann M, Detzner M et al. H3 receptor-mediated inhibition of noradrenaline release: an investigation into the involvement of Ca2+ and K+ ions, G protein and adenylate cyclase. Naunyn Schmiedeberg's Arch Pharmacol, 1994;349(4) :1~8
74． Lovenberg TW, Roland BL, Wilson ST et al. Cloning of rat histamine H3 receptor reveals distinct species. J Pharmacol Exp ther , 2000;293(3) :371~378
75． Endou M, Poli E, Levi R. Histamine H3 receptor signaling in the heart: possible involvement of Gi/Go proteins and N-type Ca2+ channels. J Pharmacol Exp ther, 1994;269(1) :221-229
76． Imamura M, Lander H.M, Levi R. Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha 2-adrenoceptors. Circ. Res, 1996; 78(3) : 475~481
77． Luo XX, Tan YH, Sheng BH. Histamine H3 receptor inhibit sympathetic neurotransmission in guinea pig myocardium. Eur J Pharmacol, 1991; 204: 311-314
78． Luo XX, Wen AD, Guo ZA, Tan YH. Direct evidence for histamine H3 receptor-mediated inhibition of norepinephrine release from sympathetic terminals of guinea pig myocardium. Zhongguo Yao Li Xue Bao, 1996; 17(5) : 425-428
79． Comzzi G, Gambarelli E, Bertaccini G et al. New aspects of the role of histamine in cardiovascular function: identification, characterization, and potential pathophysiological importance of H3 receptors. Naunyn Schmiedebergs Arch Pharmacol, 1995;351(6) : 569-575
80． Levi R, Smith NC. Histamine H(3) -receptors: a new frontier in myocardial ischemia. J Pharmacol Exp Ther, 2000 ; 292(3) :825~830．
81． Mackins CJ, Levi R. Therapeutic potential of H(3) -receptor agonists in myocardial infarction. Expert Opin Investig Drugs, 2000;9(11) :2537~ 2542
82． Hatta E, Yasuda K, Levi R. Activation of histamine H3 receptors inhibits carrier-mediated norepinephrine release in a human model of protracted myocardial ischemia. J Pharmacol Exp Ther, 1997 ;283(2) :494~500
83． Steele PA, Gibbins IL, Morris JL. Projections of intrinsic cardiac neurons to different targets in the guinea-pig heart. J Auton Nerv Syst, 1996 ; 56(3) :191~200．
84． Yeh JL, Lo YC, Wang Y, Chen LI. Cardiovascular interactions of nonivamide, glyceryl nonivamide, capsaicin analogues, and substance P antagonist in rats. Brain Res Bull, 1993; 30(5-6) : 641-648．
85． Hoover DB, Chang Y, Hancock JC et al. Actions of tachykinins within the heart and their relevance to cardiovascular disease. Jpn J Pharmacol. 2000; 84(4) :367~373
86． Alvis AG, Milesi V, Rebolledo A et al. Influence of calcitonin gene-related peptide release on pH-induced mechanical depression in rat atria. Jpn Heart J, 2001 ;42(4) :507~517
87． Griffin EC, Aiyar N, slivjak MJ et al. Effect of endotoxicosis on plasma and tissue levels of calcitonin gene-related peptide. Circ Shock, 1992;38:50~54
88． Imamura M, Neil C.E, Garbarg M et al. Histamine H3 receptor mediated inhibition of Calcitonin Gene-Related Peptide release from cardiac c
fibers. Circ Res, 1996;78(5) :863~869
89． Domeij S, Dahlqvist A, Eriksson A el al. Similar distribution of mast cells and substance P and calcitonin gene-related peptide immunoreactive nerve fibers in the adult human larynx. Ann Otol Rhinol,1996;105:825-831
90． Heine H, Forster FJ. Relationships between mast cells and preterminal nerve fibers. Z Mikrosk Anat Forsch, 1975; 89(5) : 934-937
91． Laine P, Naukkarinen A, Heikkila L. Adventitial mast cells connect with sensory nerve fibers in atherosclerotic coronary arteries. Circulation, 2000; 101(14) : 1665-1669
92． Nemmar A, Delaunois A, Beckers JF et al. Modulatory effect of imetit, a histamine H3 receptor against, on C-fibers and mast cells in rabbit lungs in vitro. Eur J Pharmacol,1999;371:23~30．
93． Chrusch C, Sharma S, Unruh H et al. Histamine H3 receptor blockade improves cardiac function in canine anaphylaxis. Am J Respir Crit Care Med,1999;160(4) : 1142-1149
94． Schworer H, Reimann A, Ramadori G et al. Characterization of histamine H3 receptors inhibiting 5-HT release from porcine enterochromaffin cells: further evidence for H3 receptor heterogeneity. Naunyn Schmiedeberg's Arch Pharmacol, 1994;350(4) :375-379
95． Fleckenstein AE, Lookingland KJ, Moore KE. Effects of histamine on 5-hydroxytryptaminergic neuronal activity in the rat hypothalamus. Eur J Pharmacol 1994;254(1-2) :35-42
96． Gietzen K. Comparison of the calmodulin antagonists compound 48/80 and calmidazolium. Biochem J, 1983; 216(3) :611-616
97． Fuder H, Ries P, Schwarz P. Histamine and serotonin released from the rat perfused heart by compound 48/80 or by allergen challenge influence noradrenaline or acetylcholine exocytotic release.Fundam Clin Pharmacol, 1994;8(6) : 477-490
98． Han X, Kobzik L, Severson D et al. Characteristics of nitric oxide-mediated cholinergic modulation of calcium current in rabbit sino-atrial node.J Physiol, 1998; 509 (Pt 3) : 741~754
99． Schlicker E, Pertz H, Bitschnau H et al. Effects of iodoproxyfan, a potent and selective histamine H3 receptor antagonist, on alpha 2 and 5-HT3 receptors. Inflamm Res, 1995; 44(7) : 296~300
100． Schlicker E, Malinowska B, Kathmann M et al. Modulation of neurotransmitter release via histamine H3 heteroreceptors. Fundam Clin Pharmacol,1994; 8(2) :128~137．
101． Gothert M, Bruss M, Bonisch H et al. Presynaptic imidazoline receptors. New developments in characterization and classification.Ann N Y Acad Sci, 1999; 881:171-184
102． Mamura M, Lander HM, Levi R. Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha2-adrenoceptors. Circ Res., 1996; 78(3) : 475-481
103． 罗晓星,谭月华.组胺H3受体激动剂与拮抗剂.中国药理学通报,1994, 10 (2) :92~96
104． Leurs R, Blandina P, Tedforkd C et al. Therapeutic potential of histamine H3 receptor agonists and antagonists. Tips,1998;19:177-183．
105． Arrang JM, Deraux B, Chodkiewicz JP et al. H3-receptor control
histamine release in human brain. J Neurochem, 1988; 51: 105~108．
106． Giacomini VA, Reis CCA.Antagonistic effect between histamine and norepinephrine on isolatated guinea pig right atrium. General pharmacol, 1986;17:219~225．
107． Luo XX, Tan YH, Sheng BH. Histamine H3 receptor inhibit sympathetic neurotransmission in guinea pig myocardium. Eur J Pharmacol,1991; 204:311-314
108． Imamura M, Poli E, Omoniyi AT et al. Unmasking of activated histamine H3 receptor in myocardial ischemia: their role as regulators of excytotic norepineohrine release.J Pharmacol Exp Ther.1994;271(3) :1259~1266
109． Imamura M, Lander HM, Levi R. Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha2-adrenoceptors. Circ Res,1996;78(3) :475~481．
110． Yoshitaka Taguchi, Takehiko Watwnabe , Hiroaki Kubota, et al. Purification of histidine decarboxylase from the liver of fetal rats and its immunochemical and immunohisto-chemical characterization. J Bio Chem,1984;259:5214~5221
111． Kimihito Maeda, Hajime Taniguchi, Isao Ohno, et al. Induction of L-histidine decarboxylase in a human mast cell line, HMC-1． Exp Hematol,1998:26:325~331
112． Hiroshi Ohtsu, Atsuo Kuramasu, Satsuki Suzuki, et al. Histidine decarboxylase expression in mast cell P815 is induced by mouse peritoneal cavity incubation.J Bio Chem,1996;271:28439~28444
113 .Garbarg M, Barbin G, Feger J, et al. Histaminergic pathway in rat brain
evidenced by lesions of the medial forebrain bundle. Science , 1974,186:833-835
114． Undem BJ,Hubbard WC,Christian EP et al.Mast cell in the guineapig superior cervical ganglion:a functional and histological assessment.J Auton Nerv Syst, 1990;30(1) :75-87
115． Happila O, Soinila S, Paivarinta H et al. Histamine-immunoreactive cells in the superior cervical ganglion and in the celiac-superior mesenteric ganglion complex of the rat. Hislochemistry, 1985;82(1) :1~3
116． Paivarinta H, Happola O, Joh TH et al. Immunocytochemical colocalization of histamine, histidine dacarboxylase, 5-hydroxytryp-tamine and tyrosine hydroxylase in the superior cervical ganglion of the rat. Histochemistry,1987;19 (6-7) :319-326
117． 向军俭,陈华粹,组胺的荧光测定法的研究.中国医学科学院学报, 1981;3 (3) :183~186
118． Lokandwala M. Inhibition of sympathetic nervous system by histamine: studies with H1-and H2-receptor antagonists. J Pharmacol Exp Ther.1978;206:115~122
119． Kimura T, Satoh S.Inhibition of cardiac sympathetic neurotransmission by histamine in the dog is mediated by Hi-receptors. J. Bri Pharma, 1983; 78:733-738
2． Black JW, Shankley NP.How does gastrin act to stimulate oxyntic cell secretion? Trends Pharmacol.Sci,1987;8:486~490
3． Arrang JM, Garbarg M, Schwartz JC. Autoinhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature, 1983;302:832~837
4． Yamasaki T, Tamai I, Matsumura Y. Activation of histamine H3 receptors inhibits renal noradrenergic neurotransmission in anesthetized dogs. Am J Physiol Regul Integr Comp Physiol, 2001; 280(5) :R 1450-1456
5． Black JW, Duncan AM, Durant J et al. Definition and antagonism of histamine H2-receptors. Nature, 1972;236:385~390
6． Raible DG, Lenahan T, Fayvilevich Y et al. Pharmacologic characterization of a novel histamine receptor on human eosinophils. Am.J.Respi.Crit.Care.Med, 1994; 149(6) : 1506-1511
7． 韩济生，神经科学纲要，北京：北京医科大学、中国协和医科大学联合 出版社,1993:419-421
8． Garbarg M, Barbin G, Feger J et al. Histaminergic pathway in rat brain evidenced by lesions of the medial forebrain bundle. Science, 1974; 186:833-835
9． Schwartz JC, Pollard H, Quach TT. Histamine as a neurotransmitter in mammalian brain: neurochemical evidence. J Neurochem, 1980; 35: 26-33
10． Hough LB. Cellular location and possible functions for brain histamine: recent progrees. Prog Neurobiol, 1988; 30: 469-505
11． Schwartz JC, Arrang JM, Garbarg M et al. Histaminergic traminergic transmission in the mammalian brain. Physiol Rev, 1991; 71: 1~15
12． Wada H, Inagaki N, Yamatodani A et al. Is the histaminergic neuron system a regulatory center for whole-brain activity? TINS,1991; 14: 415-418
13． Pollard H, Schwartz JC. Histamine neuronal pathways and their functions. Trends Neurosci, 1987; 10: 86~89
14． Alexandra AR, henk T, Edwin W et al.Pharmacological characterization of the histamine H3 receptor in the rat hippocampus Brain Res, 1998; 788; 179-186
15． Nishino S, Fujiki N, Ripley B et al. Decreased brain histamine content in hypocretin/oxexin receptor 2 mutated harcoleptic dogs. Neurosci Lett, 2001;313(2) :125~128
16． .Lozeva V, valjakka A, Anttjla E et al. Brain histamine levels and neocotical slow-wave activity in rats with portancaval anastomosis. Hepatology, 1999; 299(2) : 340-346
17． Gupta MA, Guptat AK. The use of antidepressant drugs in dermatology. J Eur Acad Dermatol Venereol, 2001; 15(6) : 512-518
18． Twmisto L, Lozeva V, Valjakka A et al. Modifying effects of histamine on circadian rhythms and neuronal excitability. Behav Brain Res, 2001; 124(2) ; 129-1351
19． Passani MB, Cangioli L, Baldi E et al. Histamine H3 receptor mediated impairmen of contextual fear conditioning and in vivo inhibition of
cholinergic transmission in the rat basolateral anygdala, Eur J neurosci, 2001; 14(9) : 1522-1532
20． Bacciottini L, passani MB, Mannaioni PF et al. Interactions between histaminergic and cholinergic systems in learning and memory. Behav Brain Res,2001; 124(2) : 183-194
21． Phjlippu A, Prast H. Importance of histamine in modnlatory processes, locomotion and memory. Behav Brain Res, 2001; 124(2) : 151-159
22． Sharma HS, Cervo S, Nararro J. Role of histamine in pathophysiology of heart stress in rats. Agents Actions Suppl, 1991; 33: 97~102
23． Bealer SL. Central neuronal histamine contributes to cardiovascular regulation. News Physiol Sci, 1999; 14:100~105
24． Mobarakeh JI, Sakurada S, Katsuyama S et al. Role of histamine H1 receptor in pain perception: a study of the receptor gene knockout mice. Eur J Pharmacol, 2000; 391(1-2) : 81-89
25． Srurman G, Freeman P, Quinn L. Histamine H1 receptor antagonists potentiate seizures in the EL(epilepsy-like) mouse model of temporal lobe epilepsy. Inflamm Res, 2001; 2: 80-81
26． Vohora D, Pal SN, Pillai KK. Histamine and selective H3 receptor ligands: a possible role in the mechanism and management of epilepsy. Pharmacol Biochem Behav, 2001; 68(4) : 735-741
27． Kjaer A, Knigge V, Jorgensen H et al. Dehydration-induced vasopressin secretion in humans: involvement of the histaminergic system. Am J Physiol Endocrinol Metab,2000; 279(6) : E1305-1310
28． Lopes JA, Ramis C, Nicolau MC et al. Histamine drugs in the rat caudate nucleus: effects on learned helplessness. Pharmacol Biochem Behav,1993;
45(2) : 275-282
29． Anthonisen M, Knigge V, Kjaer A et al. Histamine and prostaglandin interaction in the central regulation of ACTH secretion. Neuroendocrinology, 1997; 66(2) : 68-74
30． Giotti A, Guidotti A, Mannaioni PF et al. The influences of andrenotropic drugs and noradrenaline on the histamine release in cardiac anaphylaxis in vitro.J Physiol, 1966; 184(4) : 924-941
31． Triggiani M, Genovese A, Vigorito C et al. Histamine and human heart Int Arch Allergy Appl Immunol, 1985; 77(1-2) : 174-176
32． Rydzynski K, Kolago B, Zaslonka J et al. Distribution of mast cells in human heart auricles and correlation with tissue histamine. Agents Actions. 1988; 23(3-4) :273~275
33． Harvey SC. Comparative regional and subcellular distributions of histamine and norepinephrine in the hearts of rats, mice, guinea pigs, rabbits and dogs. Jpn Heart J,1978; 19(1) : 125-135
34． Rioux F, Kerouac R, St-Pierre S. Characterization of the histamine releasing effect of neurotensin in the rat heart. Peptides, 1985 ; 6(1) :121-125．
35． Yamatodani A, Maeyama K, Watanabe T et al. Tissue distribution of histamine in a mutant mouse deficient in mast cells: clear evidence for the presence of non-mast-cell histamine. Biochem Pharmacol,1982; 31(3) :305~309
36． Patella V, Marino I, Lamparter B et al. Immunologic and non-immunologic release of histamine and tryptase from human heart mast cells. Inflamm Res, 1995; 44 (Suppl) 1:S22-23
37． Masini E, Giannella E, Bianchi S et al. Histamine and lactate dehydrogenase (LDH) release in ischemic myocardium of the guinea pig. Agents Actions, 1987; 20(3-4) : 281-283
38． Negulescu P.A. and Machen T. Intracellular Ca2+ regulation during secretogogue stimulation of the pariental cell. Am.J.Physiol, 1988; 254:C130~140
39． Johnson CL, Mizoguchi H. The interaction of histamine and guanylnucleotides with cardiac adenylate cyclase and its relationship to cardiac contractility. J Pharmacol Exp Ther, 1977; 200:174~186
40． Amerinin S, Franconi F, Ledda F et al. H1 and H2 receptor in the guinea pig heart: an electrophysiological study. Agents Actions ,1982; 12:10~18
41． Chand N, Eyre P. Classification and biological distribution of histamine receptor. Agents Actions, 1975; 5:277~295
42． Luo XX, Song L, Jiang YP et al. Inhibition of sympathetic neurotransmission via NEM-sensitive H1 receptors in the guinea pig vas deferens. Meth Find Exp Clin Pharmacol, 1994; 16(3) : 185~189
43． Fatma A, Ercan Z, Purker PK. A marked H1 receptor mediated vasodilator effect of histamine in the isolated perfusal heart. Eur J Pharmacol, 1984; 97: 265-271
44． Gupta MK, Gupta P, Rezai F et al. Histamine--can it cause an acute coronary event? Clin Cardiol, 2001; 24(3) :258-259
45． Kalsner S, Ricard R. Coronary arteries of cardial patients are hyperreactivity and contain stores of amines: a mechanism coronary spasm. Science, 1984; 223:1435-1436
46． 汪昌树，刘冰怀，冠心病患者血浆组胺的变化及临床意义.广东医学,
1994; 15(3) : 154-155
47． Byron JW. Mechanism of histamine H2 receptor induced cell-cycle changes in the bone marrow stem cell. Agents Actions, 1977; 7: 209~214
48徐有恒,蒋德昭,王绮如,等,组胺H1和H2受体激动剂对多能造血 干细胞(CFU-S)细胞周期状态的影响.中国科学B辑,1988; 1: 71-73
49． Schneider E, Piquet-Pellorce C, Dy M et al. New role for histamine in interleukin-3-induced proliferation of hematopoietic stem cells. J Cell Phgsiol, 1990; 193: 337-343
50． Corbel S, Schneider E, Lemoine FM et al. Murine hematopoietic progenitors are capable of both histamine synthesis and uptake. Blood, 1995; 86: 531-535
51． Masini E, Di Bello MG, Raspanti S et al. The role of histamine in platelet aggregation by physiological and immunological stimuli. Inflamm Res, 1998; 47(5) : 211-220
52． Mannaioni PF, Pistelli A, Gambassi F et al. Definition of platelet-derived histamine-releasing factor and histaminergic receptors modulating platelet aggregation. Int Arch Allergy Appl Immunol, 1991; 94(1-4) :301-302
53． Masini E, Pistelli A, Gambassi F et al. Definition of platelet-derived histamine releasing factor (PDHRF) and histaminergic receptors modulating platelet aggregation. Adv Prostaglandin Thromboxane Leukot Res, 1991;218:533-536
54． Saxena SP, McNicol A, Brandes LJ et al. A role for intracellular histamine in collagen-induced platelet aggregation. Blood, 1990 ; 75(2) :407-414．
55． Levi R, Zavecz JH. Acceleration of idioventricular rhythms by histamine in guinea pig heart: mediation by H2 receptors. Circ Res,1979;
44(6) :847~855
56． Reinhardt D. Cardiac actions of histamine. Anaesthesist, 1979;28(2) :67~ 77
57． Levi R, Chenouda AA, Trzeciakowski JP et al. Dysrhythmias caused by histamine release in guinea pig and human hearts. Klin Wochenschr, 1982 1;60(17) :965~971
58． Kashani M, Khoyi MA, Zendehrouh R et al. The effect of histamine on the plasma potassium level and electrocardiogram of dogs. J Med, 1972; 3(2) : 103-108．
59． Doenicke A, Moss J, Toledano A et al. Administration of H1 and H2 antagonists for chemoprophylaxis: a double-blind, placebo-controlled study in healthy volunteers. J Clin Pharmacol, 1997; 37(2) : 140-146．
60． Nishimoto M, Hashimoto H, Ohmura T et al. Effects of astemizole on ventricular activation delay and RT intervals in a canine myocardial infarction model. Biol Pharm Bull, 1997; 20(9) : 1020-1023
61． Vleeming W, van Rooij HH, Werner J et al. Characterization and modulation of antigen-induced effects in isolated rat heart. J Cardiovasc Pharmacol, 1991 ; 18(4) :556-565
62． Assem ES. Anaphylactic reactions affecting the human heart. Agents Actions, 1989 ;27(1-2) :142-145
63． Steinberg MI,Holland DR.Separate receptors mediating the positive intropic and chronotropic effect of histamine in guinea pig atria. Eur J.Pharmacol, 1975 ; 34:95-104
64． Lin RY, Schwartz LB, Curry A et al. Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based
study.J Allergy Clin Immunol, 2000 ; 106(1 Pt 1) :65~71
65． Skuma I, Gross SS, Levi R. Positive intropic effect of histamine on guinea pig left atrium: H1 receptor induced stimulation of phosphoinositide turnover. J Pharmacol. Exp. Ther, 1988; 247:466-472
66． Passalacqua G, Bousquet J, Bachert C et al. The clinical safety of Hi-receptor antagonists. An EAACI position paper. Allergy, 1996; 51(10) :666~675
67． Ooie T, Saikawa T, Kara M, Ono H et al. H2-blocker modulates heart rate variability. Heart Vessels, 1999;14(3) :137~142
68． Malinowska B, Godlewski G and Schlicker E. Histamine H3 receptors-general characterization and their function in the cardiovascular system.J Physiol Pharmacol, 1998 ; 49(2) :191~211．
69． Endou M, Poli E and Levi R. Histamine H3-receptor signaling in the heart: possible involvement of Gi/Go proteins and N-type Ca++ channels. J Pharmacol Exp Ther,1994 ;269(1) :221~229
70． Malinowska B, Godlewski G and Schlicker E. Histamine H3 receptors-general characterization and their function in the cardiovascular system. J Physiol Pharmacol, 1998 ;49(2) :191-211
71． Imamura M, Seyedi N, Lander HM et al. Functional identification of histamine H3-receptors in the human heart. Circ Res, 1995;77(1) :206~ 210
72． Silver RB, Poonwasi KS , Seyedi N et al. Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings. Proc Natl Acad Sci U S A, 2002;99(1) :501-506
73． Schlicker E, Kathmann M, Detzner M et al. H3 receptor-mediated inhibition of noradrenaline release: an investigation into the involvement of Ca2+ and K+ ions, G protein and adenylate cyclase. Naunyn Schmiedeberg's Arch Pharmacol, 1994;349(4) :1~8
74． Lovenberg TW, Roland BL, Wilson ST et al. Cloning of rat histamine H3 receptor reveals distinct species. J Pharmacol Exp ther , 2000;293(3) :371~378
75． Endou M, Poli E, Levi R. Histamine H3 receptor signaling in the heart: possible involvement of Gi/Go proteins and N-type Ca2+ channels. J Pharmacol Exp ther, 1994;269(1) :221-229
76． Imamura M, Lander H.M, Levi R. Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha 2-adrenoceptors. Circ. Res, 1996; 78(3) : 475~481
77． Luo XX, Tan YH, Sheng BH. Histamine H3 receptor inhibit sympathetic neurotransmission in guinea pig myocardium. Eur J Pharmacol, 1991; 204: 311-314
78． Luo XX, Wen AD, Guo ZA, Tan YH. Direct evidence for histamine H3 receptor-mediated inhibition of norepinephrine release from sympathetic terminals of guinea pig myocardium. Zhongguo Yao Li Xue Bao, 1996; 17(5) : 425-428
79． Comzzi G, Gambarelli E, Bertaccini G et al. New aspects of the role of histamine in cardiovascular function: identification, characterization, and potential pathophysiological importance of H3 receptors. Naunyn Schmiedebergs Arch Pharmacol, 1995;351(6) : 569-575
80． Levi R, Smith NC. Histamine H(3) -receptors: a new frontier in myocardial ischemia. J Pharmacol Exp Ther, 2000 ; 292(3) :825~830．
81． Mackins CJ, Levi R. Therapeutic potential of H(3) -receptor agonists in myocardial infarction. Expert Opin Investig Drugs, 2000;9(11) :2537~ 2542
82． Hatta E, Yasuda K, Levi R. Activation of histamine H3 receptors inhibits carrier-mediated norepinephrine release in a human model of protracted myocardial ischemia. J Pharmacol Exp Ther, 1997 ;283(2) :494~500
83． Steele PA, Gibbins IL, Morris JL. Projections of intrinsic cardiac neurons to different targets in the guinea-pig heart. J Auton Nerv Syst, 1996 ; 56(3) :191~200．
84． Yeh JL, Lo YC, Wang Y, Chen LI. Cardiovascular interactions of nonivamide, glyceryl nonivamide, capsaicin analogues, and substance P antagonist in rats. Brain Res Bull, 1993; 30(5-6) : 641-648．
85． Hoover DB, Chang Y, Hancock JC et al. Actions of tachykinins within the heart and their relevance to cardiovascular disease. Jpn J Pharmacol. 2000; 84(4) :367~373
86． Alvis AG, Milesi V, Rebolledo A et al. Influence of calcitonin gene-related peptide release on pH-induced mechanical depression in rat atria. Jpn Heart J, 2001 ;42(4) :507~517
87． Griffin EC, Aiyar N, slivjak MJ et al. Effect of endotoxicosis on plasma and tissue levels of calcitonin gene-related peptide. Circ Shock, 1992;38:50~54
88． Imamura M, Neil C.E, Garbarg M et al. Histamine H3 receptor mediated inhibition of Calcitonin Gene-Related Peptide release from cardiac c
fibers. Circ Res, 1996;78(5) :863~869
89． Domeij S, Dahlqvist A, Eriksson A el al. Similar distribution of mast cells and substance P and calcitonin gene-related peptide immunoreactive nerve fibers in the adult human larynx. Ann Otol Rhinol,1996;105:825-831
90． Heine H, Forster FJ. Relationships between mast cells and preterminal nerve fibers. Z Mikrosk Anat Forsch, 1975; 89(5) : 934-937
91． Laine P, Naukkarinen A, Heikkila L. Adventitial mast cells connect with sensory nerve fibers in atherosclerotic coronary arteries. Circulation, 2000; 101(14) : 1665-1669
92． Nemmar A, Delaunois A, Beckers JF et al. Modulatory effect of imetit, a histamine H3 receptor against, on C-fibers and mast cells in rabbit lungs in vitro. Eur J Pharmacol,1999;371:23~30．
93． Chrusch C, Sharma S, Unruh H et al. Histamine H3 receptor blockade improves cardiac function in canine anaphylaxis. Am J Respir Crit Care Med,1999;160(4) : 1142-1149
94． Schworer H, Reimann A, Ramadori G et al. Characterization of histamine H3 receptors inhibiting 5-HT release from porcine enterochromaffin cells: further evidence for H3 receptor heterogeneity. Naunyn Schmiedeberg's Arch Pharmacol, 1994;350(4) :375-379
95． Fleckenstein AE, Lookingland KJ, Moore KE. Effects of histamine on 5-hydroxytryptaminergic neuronal activity in the rat hypothalamus. Eur J Pharmacol 1994;254(1-2) :35-42
96． Gietzen K. Comparison of the calmodulin antagonists compound 48/80 and calmidazolium. Biochem J, 1983; 216(3) :611-616
97． Fuder H, Ries P, Schwarz P. Histamine and serotonin released from the rat perfused heart by compound 48/80 or by allergen challenge influence noradrenaline or acetylcholine exocytotic release.Fundam Clin Pharmacol, 1994;8(6) : 477-490
98． Han X, Kobzik L, Severson D et al. Characteristics of nitric oxide-mediated cholinergic modulation of calcium current in rabbit sino-atrial node.J Physiol, 1998; 509 (Pt 3) : 741~754
99． Schlicker E, Pertz H, Bitschnau H et al. Effects of iodoproxyfan, a potent and selective histamine H3 receptor antagonist, on alpha 2 and 5-HT3 receptors. Inflamm Res, 1995; 44(7) : 296~300
100． Schlicker E, Malinowska B, Kathmann M et al. Modulation of neurotransmitter release via histamine H3 heteroreceptors. Fundam Clin Pharmacol,1994; 8(2) :128~137．
101． Gothert M, Bruss M, Bonisch H et al. Presynaptic imidazoline receptors. New developments in characterization and classification.Ann N Y Acad Sci, 1999; 881:171-184
102． Mamura M, Lander HM, Levi R. Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha2-adrenoceptors. Circ Res., 1996; 78(3) : 475-481
103． 罗晓星,谭月华.组胺H3受体激动剂与拮抗剂.中国药理学通报,1994, 10 (2) :92~96
104． Leurs R, Blandina P, Tedforkd C et al. Therapeutic potential of histamine H3 receptor agonists and antagonists. Tips,1998;19:177-183．
105． Arrang JM, Deraux B, Chodkiewicz JP et al. H3-receptor control
histamine release in human brain. J Neurochem, 1988; 51: 105~108．
106． Giacomini VA, Reis CCA.Antagonistic effect between histamine and norepinephrine on isolatated guinea pig right atrium. General pharmacol, 1986;17:219~225．
107． Luo XX, Tan YH, Sheng BH. Histamine H3 receptor inhibit sympathetic neurotransmission in guinea pig myocardium. Eur J Pharmacol,1991; 204:311-314
108． Imamura M, Poli E, Omoniyi AT et al. Unmasking of activated histamine H3 receptor in myocardial ischemia: their role as regulators of excytotic norepineohrine release.J Pharmacol Exp Ther.1994;271(3) :1259~1266
109． Imamura M, Lander HM, Levi R. Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha2-adrenoceptors. Circ Res,1996;78(3) :475~481．
110． Yoshitaka Taguchi, Takehiko Watwnabe , Hiroaki Kubota, et al. Purification of histidine decarboxylase from the liver of fetal rats and its immunochemical and immunohisto-chemical characterization. J Bio Chem,1984;259:5214~5221
111． Kimihito Maeda, Hajime Taniguchi, Isao Ohno, et al. Induction of L-histidine decarboxylase in a human mast cell line, HMC-1． Exp Hematol,1998:26:325~331
112． Hiroshi Ohtsu, Atsuo Kuramasu, Satsuki Suzuki, et al. Histidine decarboxylase expression in mast cell P815 is induced by mouse peritoneal cavity incubation.J Bio Chem,1996;271:28439~28444
113 .Garbarg M, Barbin G, Feger J, et al. Histaminergic pathway in rat brain
evidenced by lesions of the medial forebrain bundle. Science , 1974,186:833-835
114． Undem BJ,Hubbard WC,Christian EP et al.Mast cell in the guineapig superior cervical ganglion:a functional and histological assessment.J Auton Nerv Syst, 1990;30(1) :75-87
115． Happila O, Soinila S, Paivarinta H et al. Histamine-immunoreactive cells in the superior cervical ganglion and in the celiac-superior mesenteric ganglion complex of the rat. Hislochemistry, 1985;82(1) :1~3
116． Paivarinta H, Happola O, Joh TH et al. Immunocytochemical colocalization of histamine, histidine dacarboxylase, 5-hydroxytryp-tamine and tyrosine hydroxylase in the superior cervical ganglion of the rat. Histochemistry,1987;19 (6-7) :319-326
117． 向军俭,陈华粹,组胺的荧光测定法的研究.中国医学科学院学报, 1981;3 (3) :183~186
118． Lokandwala M. Inhibition of sympathetic nervous system by histamine: studies with H1-and H2-receptor antagonists. J Pharmacol Exp Ther.1978;206:115~122
119． Kimura T, Satoh S.Inhibition of cardiac sympathetic neurotransmission by histamine in the dog is mediated by Hi-receptors. J. Bri Pharma, 1983; 78:733-738